Genes in panel

Hereditary ataxia - adult onset

Gene: TMEM106B

Green List (high evidence)

TMEM106B (transmembrane protein 106B)
EnsemblGeneIds (GRCh38): ENSG00000106460
EnsemblGeneIds (GRCh37): ENSG00000106460
OMIM: 613413, Gene2Phenotype
TMEM106B is in 6 panels

3 reviews

Arina Puzriakova (Genomics England Curator)

I don't know

Comment on list classification: This gene has been flagged for review at the next GMS panel update (added 'for-review tag) as there is only enough evidence for TMEM106B to be rated AMBER on this panel.

Only 2/6 cases present ataxia, which is mild in one individual. Cases are more likely to be recognised for the leukodystrophy feature of this disease presentation; however, this could be reviewed if evidence emerges of a more prominent ataxic phenotype.
Created: 12 Nov 2020, 5:21 p.m. | Last Modified: 12 Nov 2020, 5:21 p.m.
Panel Version: 2.16
Associated with relevant phenotype in OMIM, and is a 'probable' gene for 'TMEM106B related hypomyelinating leukodystrophy' in Gene2Phenotype.

Recurrent variant c.754G>A p.(Asp252Asn) identified in 6 unrelated families from different ethnicities. Clinical characteristics include hypomyelinating leukodystrophy (6/6), nystagmus (6/6), hypotonia (5/6), cognitive impairment (5/6), movement disorder (3/6) and seizures (2/6).

Only 2 individuals present gait ataxia and intention tremor (mild/minimal in one case), with only mild cerebellar atrophy identified in one patient on brain MRI.
Created: 12 Nov 2020, 5:19 p.m. | Last Modified: 12 Nov 2020, 5:19 p.m.
Panel Version: 2.15

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Leukodystrophy, hypomyelinating, 16 OMIM:617964

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Louise Daugherty (Genomics England Curator)

I don't know

Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group.
Created: 15 Apr 2019, 10:21 a.m.

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

Multiple cases reported in the two papers all associated with a single recurrent de novo variant c.754G>A p.(Asp252Asn)
Created: 15 Apr 2019, 10:06 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hypomyelinating leukodystrophy 16, 617964

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • NHS GMS
  • Wessex and West Midlands GLH
Phenotypes
  • Leukodystrophy, hypomyelinating, 16, OMIM:617964
  • Leukodystrophy, hypomyelinating, 16, MONDO:0054791
Tags
missense for-review
OMIM
613413
Clinvar variants
Variants in TMEM106B
Penetrance
None
Mode of Pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Panels with this gene

History Filter Activity

12 Nov 2020, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: TMEM106B were changed from Leukodystrophy, hypomyelinating, 16 OMIM:617964 to Leukodystrophy, hypomyelinating, 16, OMIM:617964; Leukodystrophy, hypomyelinating, 16, MONDO:0054791

12 Nov 2020, Gel status: 3

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: tmem106b has been classified as Green List (High Evidence).

12 Nov 2020, Gel status: 3

Added Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag missense tag was added to gene: TMEM106B. Tag for-review tag was added to gene: TMEM106B.

12 Nov 2020, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: TMEM106B were changed from Hypomyelinating leukodystrophy 16, 617964 to Leukodystrophy, hypomyelinating, 16 OMIM:617964

27 Apr 2019, Gel status: 3

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: TMEM106B was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

27 Apr 2019, Gel status: 3

Set mode of pathogenicity

Louise Daugherty (Genomics England Curator)

Mode of pathogenicity for gene: TMEM106B was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

27 Apr 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: tmem106b has been classified as Green List (High Evidence).

15 Apr 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Added phenotypes Hypomyelinating leukodystrophy 16, 617964 for gene: TMEM106B

14 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to TMEM106B.

14 Apr 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: TMEM106B was added gene: TMEM106B was added to Hereditary ataxia - adult onset. Sources: Wessex and West Midlands GLH Mode of inheritance for gene: TMEM106B was set to